There are 10-15,000 malignant brain tumors diagnosed each year. The most common of these are glioblastomas. Numerous treatments involving surgery, chemotherapy, and radiation are of palliative benefit only. We study the adoptive immunotherapy of malignant brain tumors with interleukin-2 (IL-2), lymphokine-activated killer (LAK) cells, and tumor infiltrating lymphocytes (TILs) in animal models and in patients. In the 9L gliosarcoma rat model, we studied the efficacy of parenteral IL-2 and its effect on the blood-brain barrier of normal and neoplastic tissue, and in the C3H mouse we studied the cytolytic activity of LAK against metastases in the brain. In patients with extracranial cancer, we examined the kinetics of IL-2 in the cerebrospinal fluid as compared to serum, and in patients with gliomas we investigated the cerebral toxicity of parenteral IL-2. We are currently completing our studies with IL-2 and LAK cells, and are expanding our efforts with TILs. In animals models of primary and metastatic brain tumors, we have raised TILs against tumors in the subcutaneous space; these cells will then be used to treat animals with intracerebral tumors and to study trafficking across the blood-brain barrier with (111)Indium labeled cells. In patients, we are raising TILs from brain tumors grown in the subcutaneous space. These have been expanded in vitro with IL-2, and injected parenterally into mice to study lymphocyte trafficking and efficacy against intracerebral tumors. In patients we have raised TILs from fresh specimens sent from the operating room. This creates the possibility of proceeding with Phase I clinical trials based on the final outcome of our laboratory efforts. Lastly, we are investigating the regulation of major histocompatibility antigens of brain tumors in vitro by interleukins, interferons, and tumor factor.